Case: A 31-year-old gravida 2 parity 1 presented at 33 weeks gestation with 2 days of vomiting and decreased oral intake. History was significant for schizophrenia on recently up-titrated clozapine 300mg daily and overt diabetes in pregnancy on metformin with large-for-gestational-age fetus. She was clinically dehydrated with severe metabolic acidosis (pH 7.15, HCO3 6 mmol/L) and ketosis with ketones 6.5 mmol/L (<1.5). Blood glucose was 7.7 mmol/L, lactate 1.4mmol/L (<2.0) and HbA1c 6.2%. Infectious screen was normal. Clozapine level was supratherapeutic 611ug/L (<600). Intravenous fluids were commenced for diagnosis of starvation ketosis. However after persistent ketosis, euglycaemic diabetic ketoacidosis was diagnosed, insulin dextrose infusion was commenced, and clozapine and metformin were withheld. Though ketosis improved, CTG became abnormal with no variability or accelerations. The woman underwent emergency caesarean section with no steroid cover and a live 2805g neonate was born in poor condition requiring resuscitation and respiratory support. She recovered well with cessation of the insulin infusion day one postoperatively and clozapine subsequently restarted. Post-partum glucose tolerance test was positive for diabetes and pancreatic autoantibodies for Type-1-diabetes-mellitus were negative.
Discussion: In this case, euglycaemic diabetic ketoacidosis (DKA) is the likely diagnosis with pregnancy, clozapine and reduced oral intake or infection being contributing factors. Pregnancy is associated with maternal insulin resistance and ketogenesis, progressively worsening in third trimester. DKA in pregnancy has high maternal and fetal morbidity and mortality (15% fetal mortality, 46% preterm birth)1. Clozapine and second generation antipsychotics can produce insulin resistance and have been associated with DKA outside pregnancy2. Starvation and illness can also exacerbate ketosis.
Conclusion: It is imperative that metabolic acidosis in pregnancy is investigated and managed promptly as recognition of euglycaemic DKA is vital due to the risk of maternal and fetal morbidity. Further, clozapine therapy in pregnancy warrants close observation particularly in the setting of diabetes due to the potential risk of DKA.
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